This invention relates to treating diseases characterized by an undesirable buildup of .beta.-amyloid protein (".beta.-amyloid").
.beta.-amyloid is a well characterized protein that is the primary constituent of senile plaques and cerebrovascular deposits in Alzheimer's disease and Down's syndrome. The form of .beta.-amyloid that is most prevalent in senile plaques contains 40-42 amino acids, but various other .beta.-amyloid forms are known, ranging from 28-43 amino acids in length.
.beta.-amyloid protein is encoded as part of a message that encodes a much larger precursor (the amyloid precursor protein, APP), carboxy terminal fragments of which are neurotoxic to hippocampal neurons in culture. Yankner et al., 245 Science 417, 1989. Whitson et al., 243 Science 1488, 1989, however, describe a peptide homologous to .beta.-amyloid which increases the survival of young undifferentiated hippocampal neurons in cell culture.
Patients with Alzheimer's disease exhibit reduced levels of neurotransmitter peptides: Beal et al., Science (1985) 229:289-291 (receptors for somatostatin); Davis et al., Nature (1980) 288:279-280 and Rossor et al., Neurosci. Ltrs. (1980) 20:373-377 (somatostatin); Whitehouse, et al. Anal. Neurol. (1981) 10:122-126 (acetyl choline); Quigley et al., Neurosci (1986) 17:70a and Quigley et al. (1991) Neurosci 41:41-60 (Substance P); Adolfsson et al. (1978) In "Alzheimer's Disease, Senile Dementia and Related Disorders (Aging)" Ed. Katzman et al., Vol. 7, pp. 441-451 New York, Rauer (noradrenalin).